Inconsistent results have been found in the studies evaluating the effect of both total and partial sleep deprivation (SD) on mood in healthy subjects and a few variables have been analyzed as possible predictors. In the present study, we examined whether circadian preference modifies the effect of SD on mood changes in healthy subjects. Sample consisted of 60 healthy volunteers (including 30 morningness and 30 eveningness subjects). Then, the two groups were again divided into two groups for two SD procedures. Fifteen morningness and 15 eveningness chronotypes were total sleep deprived and 15 morningness and 15 eveningness subjects were partial sleep deprived. The mood changes were evaluated before and after SD using Profile of Mood States. Two main results were obtained from our study: a significant increase in depression subscale in morningness chronotypes and a significant decrease in depression subscale score after total SD (TSD) in eveningness chronotypes. The changes in depression-dejection scores of eveningness chronotypes after total (P < 0.01) and partial SD (P < 0.01) were significantly different from changes in morningness chronotypes after TSD. Our results suggest that the effect of SD on mood in normal subjects is related to their circadian preferences. The morningness or eveningness characteristics of the shift workers have significant impact on their mood states. Therefore, adjusting the work schedule with the morningness and eveningness characteristics of the workers may improve their mood alterations.